Abstract
Breast cancer is the most commonly diagnosed and the second leading cause of cancer-related mortality among women worldwide. miR-518f-5p has been shown to modulate the expression of the metastasis suppressor CD9 in prostate cancer. However, the role of miR-518f-5p and CD9 in breast cancer is unknown. Therefore, this study aimed to elucidate the role of miR-518f-5p and the mechanisms responsible for decreased CD9 expression in breast cancer, as well as the role of CD9 in de novo tumor formation and metastasis. miR-518f-5p function was assessed using migration, adhesion, and proliferation assays. miR-518f-5p was overexpressed in breast cancer cell lines that displayed significantly lower CD9 expression as well as less endogenous CD9 3′UTR activity, as assessed using qPCR and dual luciferase assays. Transfection of miR-518f-5p significantly decreased CD9 protein expression and increased breast cell migration in vitro. Cd9 deletion in the MMTV/PyMT mouse model impaired tumor growth, but had no effect on tumor initiation or metastasis. Therefore, inhibition of miR-518f-5p may restore CD9 expression and aid in the treatment of breast cancer metastasis.
Highlights
Breast cancer is a complex, heterogeneous disease that is expected to account for 30% of all new cancer cases in females in 2020, making it the most prevalent cancer among women in the United States [1].Cancers 2020, 12, 795; doi:10.3390/cancers12040795 www.mdpi.com/journal/cancersAt an estimated 15% of female cancer-related deaths in 2020, it is the second highest cause of cancer-related mortality [1]
This study provides the first evidence that miR-518f-5p modulates migration in breast cell lines
Bioinformatics analysis showed that miR-518f-5p is predicted to regulate an array of pathways which play an important role in cancer progression and miR-518f-5p expression was shown to correlate with poor patient outcome
Summary
Breast cancer is a complex, heterogeneous disease that is expected to account for 30% of all new cancer cases in females in 2020, making it the most prevalent cancer among women in the United States [1].Cancers 2020, 12, 795; doi:10.3390/cancers12040795 www.mdpi.com/journal/cancersAt an estimated 15% of female cancer-related deaths in 2020, it is the second highest cause of cancer-related mortality [1]. New and more efficacious therapies that target breast cancer progression are required to lower the mortality rates associated with breast cancer and increase patient quality of life. This requires research that increases our understanding of cancer progression and metastasis. Studies in breast cancer have shown that patients with high CD9 expression have significantly higher overall and relapse-free survival, and those with metastatic disease with high CD9 levels respond better to therapy [3,4,5,6]. Low CD9 expression in primary breast tumors is associated with higher metastatic potential, and CD9 gene expression is commonly downregulated in lymph node metastases compared to primary breast tumors [7,8]
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